The immunoglobulin kappa (kappa) gene promoter was activated by a "neutral" enhancer derived from Harvey murine sarcoma virus (HaMuSV) in immunoglobulin-producing myeloma cells, regardless of the enhancer's orientation or position in the vector. In one fibroblast line (3T3) the immunoglobulin kappa gene promoter was completely inactive when linked to the HaMuSV enhancer, whereas in mouse L cells, promoter activity was observed only with the HaMuSV enhancer in tandem with the immunoglobulin kappa gene promoter. The differential behavior of the gene promoter, when activated by a neutral enhancer in these three murine cell lines, suggests that promoter sequences contribute to the tissue-specific expression of this gene.